Properties of Torpedo electric organ muscarinic receptors

1. Synaptosomes isolated from Torpedo electric organ, and incubated with [1-14C]acetate to prelabel the ACh stores, rapidly lost [14C]ACh when depolarized with high K+. The extent of this loss was typically about 10%. 2. The K+-stimulated loss (release) of [14C]ACh was inhibited by the muscarinic agonist, oxotremorine (5 microM), and effect antagonized by two muscarinic antagonists, atropine at 5 nM and pirenzepine at 2 microM. 3. Ligand-binding studies on membranes isolated from Torpedo electric organ show that the muscarinic receptors are qualitatively the same as established in other tissues. Thus antagonist binding was to a single class of sites, with nM affinity and an insensitivity to GTP. By contrast agonist binding was more complex (multi-site), with microM affinity and was sensitive to GTP (apparent lowered affinity). 4. Binding affinities of a variety of different ligands of various categories, including antidepressant drugs, were similar in Torpedo to rat brain indicating a quantitative similarity between the receptors in these diverse tissues.